Tachyphylaxis occurs from the channels open state A, top, ASIC1a channels were repeatedly activated by pH 5 for 10 s (left) or 60 s (right). In both conditions, channels were allowed to recover at pH 7.4 for 60 s. Bottom, current amplitudes were normalized to the first amplitude. Continuous lines represent fits to a single exponential function. 10 s application, n = 10; 60 s application, n = 8. Bi, comparison of desensitization of wt ASIC1a with mutant SQL(83-85)-PLM. The desensitization time constant of ASIC1a wt and SQL-PLM were 1.9 ± 0.1 s (n = 10) and 0.17 ± 0.02 s (n = 10), respectively. ii, representative current traces of repetitive activation with pH 5 of mutant SQL-PLM. iii, current amplitudes were normalized to the first amplitude. For ASIC1a, continuous line represents a fit to a single exponential function. **P < 0.001 by t test. If not specified differently, n = 10 for ASIC1a wt and n = 11 for ASIC1a SQL-PLM.